ML358 is a first in class, selective small molecule inhibitor of the SKN-1 pathway with IC50 of 0.24 uM.
ML358 shows inactivity against Nrf2, the homologous mammalian detoxification pathway, and is not toxic to C. elegans (LC50 > 64 uM) and Fa2N-4 immortalized human hepatocytes (LC50 > 5.0 uM).
ML358 sensitizes the model nematode C. elegans to oxidants and anthelmintics.
ML358 exhibits good solubility, permeability, and chemical and metabolic stability in human and mouse liver microsomes.
ML358 a valuable chemical probe to study regulation and function of SKN-1 in vivo.
